An audit of calcium supplement prescribing at an urban general practice in the UK

Osteoporosis is a major cause of morbidity and mortality in people over the age of 50. Calcium and vitamin D supplements are recommended as adjuncts to other pharmacological therapies for osteoporosis in this group. Recent evidence suggests that, whilst calcium supplements co-administered with vitamin D may reduce osteoporotic fracture risk, calcium supplements given alone have little, if any, effect on fracture risk, and are associated with a 30% increase in the risk of myocardial infarction.

Audit standard: That no patients over the age of 40 should be prescribed calcium supplements without vitamin D.Aim: This audit aimed to identify all patients over the age of 40 registered at an urban general practice who had been prescribed calcium supplements without vitamin D.Method: The general practice’s electronic database was searched for patients over the age of 40 who had been issued with a prescription for calcium supplements in the year preceding the audit. Patients were excluded if they had also been prescribed vitamin D supplements.Results: Of 9689 patients registered with the general practice, 11 patients met the search criteria. Nine patients were female; the mean age was 80 years (range 50-92 years); and the mean daily dose of elemental calcium was 764 mg (range 500-1200 mg). Indications for calcium supplementation varied considerably, and were not stated for three patients. No patients had suffered a significant cardiovascular event during the period that they had been prescribed calcium supplements.
Discussion and implementation of change: Very few patients at the practice had been prescribed calcium supplements without vitamin D. The results of this audit were presented to the practice team, who agreed with the plan that all 11 patients should have their prescription reviewed, and that doctors should clearly write the indications for supplementation in the medical notes. A repeat audit was planned for one year’s time.

Introduction

Osteoporosis is a systemic skeletal disease characterised by low bone density and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture [1]. It is a major cause of morbidity and mortality in older people: 54% of women aged 50 years or older will have an osteoporotic fracture during their lifetime [2].

Calcium supplements, with or without vitamin D, are commonly used by people over the age of 50 for primary and secondary prevention of osteoporotic fragility fractures [3]. This practice is widely advocated, with most professional guidelines [4-9] recommending the prescription of calcium and vitamin D supplements both to achieve specified minimum daily intake levels, which are otherwise rarely met in this age group [9], and as adjuncts to other pharmacological interventions for osteoporosis, such as bisphosphonates.

Calcium supplements, with or without vitamin D, have been shown to modestly increase bone mineral density in both men and women [10-13]; a meta-analysis of randomised controlled trials [10] suggested an overall 2.05% increase in total bone density (95% confidence interval [CI] 0.24-3.86). The effect of calcium alone on fracture risk, however, is marginal at best. A systematic review by MacLean et al. [14] found no significant difference between calcium alone and placebo in preventing fractures of all types in postmenopausal women, and insufficient evidence to evaluate an effect in men. A recent meta-analysis [12] concluded that the relative risk for fracture with calcium alone in men and women was 0.90 (95% CI 0.80-1.00), but this did not include a modestly large trial with negative results [15]. Calcium in combination with vitamin D may be more effective, with significant effects demonstrated by three meta-analyses [12,16,17]: relative risk for fractures of all types varied from 0.87 (95% CI 0.77-0.97) (12) to 0.92 (95% CI 0.86-0.99) [17], and for hip fractures varied from 0.84 (95% CI 0.73-0.96) (16) to 0.87 (95% CI 0.75-0.99) [12].

Evidence has recently emerged that calcium supplements without vitamin D are associated with increased rates of cardiovascular events. A five-year randomised controlled trial of calcium supplements in 1471 postmenopausal women reported a significantly increased risk of myocardial infarction (MI) in the calcium group relative to the control group (relative risk [RR] 2.12, 95% CI 1.01-4.47) [18]. This was followed by a meta-analysis by Bolland et al. [3], who reviewed 11 randomised controlled trials of calcium supplements (≥500 mg/day, without vitamin D) in men and women aged 40 years or older (total number of participants: 11 921). From the five studies contributing patient-level data, they calculated a hazard ratio for MI of 1.31 (95% CI 1.02-1.67), with non-significant increases in the incidence of stroke (1.20, 95% CI 0.96-1.50), death (1.09, 95% CI 0.96-1.23), and the composite end point of MI, stroke, or sudden death (1.18, 95% CI 1.00-1.39). The risk of MI with calcium tended to be greater in those with dietary calcium intake above the median, but was independent of age, sex, and type of supplement. The meta-analysis of trial-level data showed similar results: pooled relative risk for MI was 1.27 in the calcium group (95% CI 1.01-1.59), with no significant increase in incidence of stroke, death, or the composite end point.

The authors concluded that calcium supplements (without co-administered vitamin D) are associated with about a 30% increased risk of MI and smaller, non-significant, increases in the risk of stroke and mortality. They calculated that treating 1000 people with calcium for five years would cause an additional 14 MIs and prevent 26 fractures. This contrasts with the results of observational studies suggesting that high dietary calcium might protect against cardiovascular disease [19-21]; Bolland et al. [3] speculate that this may be because ingestion of equivalent doses of calcium from dairy products has a much smaller effect on serum calcium levels than calcium supplements.

The meta-analysis by Bolland et al. [3] excluded studies that compared co-administered calcium and vitamin D supplements with placebo; the results therefore may not apply to combined calcium and vitamin D supplements. Indeed, a randomised controlled trial of 36 282 postmenopausal women showed neither an increase nor a decrease in coronary risk with calcium and vitamin D supplementation over a seven-year use period [22]. However, most of the participants in this study were taking personal, non-protocol calcium supplements at study entry. Since the following audit was initiated, Bolland et al. have published a second meta-analysis which showed that calcium supplements co-administered with vitamin D do, in fact, significantly increase the risk of both MI (RR 1.21, 95% CI 1.01-1.44) and stroke (1.20, 95% CI 1.00-1.43) [23].

In summary, for both men and women, calcium supplements given alone have little, if any, effect on osteoporotic fracture risk, and are associated with about a 30% increase in the risk of MI in people over the age of 40. Calcium supplements co-administered with vitamin D reduce fracture risk by 8-13%, but may also increase cardiovascular risk by a similar degree to calcium supplements alone.

Standard

On the basis of the above evidence, the author approached a GP at an urban general practice in the UK with a view to auditing the prescription of calcium supplements at that practice. We reached a consensus that best practice is to always prescribe calcium supplements with vitamin D, and agreed on the following audit standard: that no patients over the age of 40 should be prescribed calcium supplements without vitamin D. This consensus standard was primarily based on the results of the above literature review, apart from the second meta-analysis by Bolland et al. [23], which had not yet been published. It is also in agreement with most professional guidelines [4-9], which recommend co-prescription of calcium and vitamin D supplements, although they do not yet incorporate the postulated risks of using calcium supplements alone.

Aim

The aim of this audit was to identify all patients over the age of 40 registered at an urban general practice in the UK who had been issued with a prescription for calcium supplements without vitamin D in the year preceding the audit (i.e. the time period 7 September 2009 to 6 September 2010).

Method

The general practice’s electronic patient database was searched for patients meeting both of the following criteria:
• Aged over 40 years. (This age group was selected because the evidence for an association between calcium supplements and increased risk of MI applies only to people aged 40 years or older.)
• Had been issued with a prescription for any drug in the class “calcium supplements” [BNF section 9.5.1.1] during the time period 7 September 2009 to 6 September 2010. (This time period was chosen on the assumption that anyone last issued with a prescription for calcium supplements within the year preceding the audit might still be taking them at the time of the audit, whereas anyone last issued with a prescription more than a year before then would probably not be taking them any more.)

The notes of eligible patients were inspected. Patients were excluded if they had been prescribed any type of vitamin D supplement [BNF section 9.6.4] with their calcium supplements during the time period 7 September 2009 to 6 September 2010. The following data were extracted for all remaining patients:
• Patient number.
• Sex.
• Date of birth.
• Calcium supplement prescribed and dose.
• Indication for calcium supplementation.
• Date of issue of first prescription and prescribing GP.
• Date of issue of most recent prescription and prescribing GP.
• Occurrence of any cardiovascular events (MI, stroke, or sudden death) between the date of issue of the first prescription for calcium supplements and 7 September 2010.

The following data were calculated for the patients:
• Age on 6 September 2010.
• Daily dose of elemental calcium.
• Estimated duration of calcium supplementation therapy, calculated as the time between the date of issue of the first prescription for calcium supplements and 6 September 2010.

Results

9689 patients were registered with the general practice at the time of the audit. The initial database search returned 13 patients, of whom 12 were registered patients and one was a temporary patient. Two patients had been prescribed a vitamin D supplement (alfacalcidol and colecalciferol, respectively) with their calcium supplements, and were therefore excluded. Anonymised data for the remaining 11 patients are presented in table 1.

Table 1. Characteristics of the 11 patients eligible for inclusion in this audit.

The majority of patients (9 out of 11) were female; the mean age was 80 years (range 50-92 years). All patients had been prescribed calcium carbonate, with one also prescribed calcium gluconate. The mean daily dose of elemental calcium was 764 mg (range 500-1200 mg). Indications for calcium supplementation varied: four patients had osteoporosis or osteopenia, of whom three had suffered fragility fractures; single patients were individually prescribed calcium under the headings of lumbar spinal stenosis, menopause, omeprazole use, and vitamin D deficiency (interestingly, this patient did not seem to have been prescribed vitamin D); and for three patients there was no clear indication, although two of them were noted to have had a fall just prior to the date of issue of their first prescription. The mean estimated duration of calcium supplementation therapy was 4.4 years (range 0.3-19.6 years), with all but one of the practice’s doctors having issued a prescription for calcium supplements at some point. Happily, no patients had had any significant cardiovascular events during the time that they were prescribed calcium supplements.

Discussion

The results of this audit show that very few patients over the age of 40 had been prescribed calcium supplements without vitamin D during the year preceding the audit at this UK urban general practice. Whilst most of these patients had probably been prescribed calcium supplements for primary or secondary prevention of osteoporotic fragility fractures, in several patients this indication was not clear from the notes.

Implementation of change

The above results, with the addition of patient-identifiable information, were reported by the author at a fortnightly meeting of the general practice team. Team members were also informed of the risks and lack of efficacy of calcium supplements without co-administered vitamin D. After discussion, the following action plan was agreed by the team:

a) All of the 11 patients in table 1 should have their prescription reviewed, with a view to either switching to co-administered calcium and vitamin D supplements or stopping supplements altogether. Patients should either be called in to the practice for this purpose, or have a reminder added to their notes so that the prescription can be reviewed when they next attend for another reason.
b) Doctors prescribing calcium supplements with or without vitamin D should clearly write the indication for supplements in the medical notes.

The practice partners took joint responsibility for this plan. It was agreed that these changes should be implemented within one year, following which a repeat audit should be performed, using the above method. The author hopes to assist in completing this audit cycle in September 2011.

Evidence is continuing to accumulate in this field. Since the above plan was agreed, it has emerged that calcium supplements co-administered with vitamin D may increase cardiovascular risk by a similar degree to calcium supplements alone [23]. Future audit standards may therefore have to be adjusted to reflect this new evidence and any concomitant changes to professional guidelines.